Arginine modified polymeric micelles as a novel drug delivery system with enhanced endocytosis efficiency

A new drug delivery system with improved endocytosis efficiency based on arginine modified poly(ethylene glycol)- b -poly(ε-caprolactone) (PEG-PCL) diblock copolymers was developed successfully. The structures of amphiphilic copolymers were verified by proton Nuclear Magnetic Resonance ( 1 H NMR), Fourier Transform Infrared (FTIR) and Gel Permeation Chromatography (GPC). The amphiphilic copolymers could self-assemble into spherical micelles with critical micelle concentration (CMC) at approximately 0.03   mg/mL. Biocompatibility, cellular internalization efficiency and in vitro antitumor effect of the polymeric micelles were studied. Results showed that drug-free micelles were nontoxic to cells. The Confocal Laser Microscopy (CLSM) and the flow cytometry as well as the antitumor activity tests all revealed that drug-loaded micelles modified by arginine groups (guanidino) exhibited higher endocytosis efficiency than those without modification, resulting in a lower IC 50 value to kill tumor cells and meanwhile averting the “competitive binding” problem. Also, in vivo results demonstrated that arginine modified polymeric micelles could deliver the drug to tumor site more efficiently than ones without any modification, thus indicating guanidino in polymeric micelles could benefit the internalization of micelles to fully exert the function of killing tumors. In general, guanidinylation strategy in this splendid novel micelle system has a great potential to improve the therapeutic effect of nanoparticle-based drug delivery system for cancer therapy in the future.